A Neoadjuvant, Randomized, Open-Label Phase II Trial of Afatinib Versus Trastuzumab Versus Lapatinib in Patients With Locally Advanced HER2-Positive Breast Cancer
A Neoadjuvant, Randomized, Open-Label Phase II Trial of Afatinib Versus Trastuzumab Versus Lapatinib in Patients With Locally Advanced HER2-Positive Breast Cancer
复制标题
DOI：
10.1016/j.clbc.2014.11.004
复制
发表时间：
2015-04-01
影响因子：
3.1
通讯作者：
Osborne, C. Kent
中科院分区：
文献类型：
--
作者：
Rimawi, Mothaffar F.;Aleixo, Sabina B.;Osborne, C. Kent
新辅助治疗用于缩小肿瘤以便于手术。在这项II期新辅助试验中，我们比较了口服不可逆转的ErbB家族阻滞剂afatinib与拉帕替尼和曲妥珠单抗在未经治疗的局部晚期(LA)HER2阳性乳腺癌(BC)患者中的疗效和安全性。虽然招募被提前停止，但接受阿法替尼单一治疗的10名患者中有8名取得了客观反应。不良事件是可控的。背景：化疗是LA BC的标准新辅助治疗。HER2阳性BC患者需要靶向治疗。靶向HER2的曲妥珠单抗和pertuzumab与化疗一起被批准为新辅助治疗，然而，不同作用机制的治疗可能提供更广泛的活性范围。在这项研究中，我们评估了不可逆转的ErbB家族阻滞剂afatinib与曲妥珠单抗或拉帕替尼在新辅助治疗HER2阳性LA BC中的疗效和安全性。患者和方法：治疗初治、HER2阳性、IIIA、B、C期或炎症性疾病的BC患者按1：1：1随机分为三组，每日服用阿法替尼(50 Mg)、拉帕替尼(1500 Mg)或每周曲妥珠单抗(4 mg/kg负荷量，然后2 mg/kg/wk)，疗程6周，直到手术或后续新辅助治疗。主要终点是根据实体瘤反应评估标准(1.0版)的客观应答率。结果：由于患者入选缓慢，重复试验提前停止；29名患者被随机分为托法替尼(n=10)、拉帕替尼(n=8)或曲妥珠单抗(n=11)。目的观察8名服用非那替尼、6名服用拉帕替尼和4名服用曲妥珠单抗的患者的疗效。11名患者病情稳定(最佳反应)；1名服用拉帕替尼的患者和1名接受曲妥珠单抗治疗的患者病情进展。所有10名服用阿法替尼的患者都出现了与药物有关的不良反应(通常是腹泻、痤疮和甲沟炎)，而服用拉帕替尼的患者中有6名(腹泻和皮疹)，11名曲妥珠单抗治疗的患者中有5名(呕吐和关节痛)。结论：与曲妥珠单抗和拉帕替尼相比，阿法替尼在新辅助治疗HER2阳性BC方面显示出更好的临床活性，其安全性与表皮生长因子受体酪氨酸激酶抑制剂一致。
Neoadjuvant therapy is used to shrink tumors to facilitate surgery. In this phase II neoadjuvant trial we compared the efficacy and safety of the oral irreversible ErbB family blocker afatinib with lapatinib and trastuzumab, in patients with untreated, locally advanced (LA) HER2-positive breast cancer (BC). Although recruitment was stopped early, 8 of 10 patients who received afatinib monotherapy achieved objective responses. Adverse events were manageable.Background:Chemotherapy is standard neoadjuvant treatment of LA BC. Patients with HER2-positive BC require targeted therapy. Trastuzumab and pertuzumab, which target HER2, with chemotherapy are approved as neoadjuvant therapy, however, treatments with different mechanisms of action might provide a broader range of activity. In this study we evaluated the efficacy and safety of the irreversible ErbB family blocker afatinib, versus trastuzumab or lapatinib in the neoadjuvant treatment of HER2-positive, LA BC. Patients and Methods:Treatment-naive, HER2-positive BC patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to daily afatinib (50mg), lapatinib (1500 mg), or weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg/wk) for 6 weeks until surgery or follow-up neoadjuvant treatment. The primary end point was objective response rate according to Response Evaluation Criteria in Solid Tumors (version 1.0). Results:Recruitmentwas stopped early because of slow patient enrollment; 29 patientswere randomized toafatinib (n = 10), lapatinib (n = 8), or trastuzumab (n = 11). Objective response was seen in 8 afatinib-, 6 lapatinib-, and 4 trastuzumab-treated patients. Eleven patients had stable disease (best response); 1 lapatinib-and 1 trastuzumab-treated patient had progressive disease. All 10 afatinib-treated patients experienced drug-related adverse events (commonly diarrhea, dermatitis acneiform, and paronychia) versus 6 of 8 lapatinib-(diarrhea and rash) and 5 of 11 trastuzumab-treated patients (vomiting and arthralgia). Conclusion:Afatinib demonstrated clinical activity that compared favorably to trastuzumab and lapatinib for neoadjuvant treatmentofHER2-positiveBC, with a safety profile consistent with epidermalgrowth factor receptor tyrosine kinase inhibitors.